This project is designed to develop models of human diseases in small animals, primarily mice and rats. The focus has been on those diseases which have a complex genetic etiology and which also include a significant environmental component. In the rat, the emphasis has been on models for the study of rheumatoid arthritis, insulin independent diabetes mellitus, behavioral disorders as well as chemical addictions. In the mouse, models for the study of human immune disorders have been developed by making different combinations of single mutations which affect different components of the murine immune system. A secondary but critical aspect to the above studies has been the evaluation of those components which might affect reproductive efficiency. Results thus far indicate that reproductive efficiency of mice and hamsters are sensitive to seasonal differences whereas species such as rats, guinea pigs and rabbits appear be immune to these effects.